Iodoethane → Ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid

HRID 1058144

Reaktionsgleichung

Reaktionsgleichung von HRID 1058144
[O:1]=[C:2]1[C:7]2[C:8]([C:11]([OH:13])=[O:12])=[CH:9][O:10][C:6]=2[CH2:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:27][CH3:28]>CN(C)C=O>[CH2:27]([C:9]1[O:10][C:6]2[CH2:5][CH2:4][CH2:3][C:2](=[O:1])[C:7]=2[C:8]=1[C:11]([OH:13])=[O:12])[CH3:28]

Komponenten

6

Edukt 4

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 7139374-Oxo-4,5,6,7-tetrahydro-1-benzofuran-3-carboxylic acid

Produkt 1

HCID 21953055Ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acidAusbeute 86,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a stirred mixture of 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (640 g, 3.55 mol), potassium carbonate (1.7 kg, 10.65 mol) and cesium carbonate (100 g, 0.32 mol) in N,N-dimethylformamide (9.0 L) is added iodoethane (1250 g, 8.01 mol). The mixture is heated at 60° C. for 2 h. After cooling to ambient temperature, the mixture is filtered, the solid is rinsed with ethyl acetate, and the filtrate concentrated in vacuo. Water (2 L) is added then extracted with ethyl acetate (2×2 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (642 g). A mixture of this ester (640 g, 3.07 mol) and ammonium acetate (426 g, 5.53 mol) in N,N-dimethylformamide (320 mL) is heated to 100° C. for 2 h. The reaction mixture is concentrated in vacuo , ice water (2.5 L) is added, and extracted with dichloromethane (2×3 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (357 g). A mixture of this ester (170 g, 0.82 mol) in ethyl alcohol (250 mL) and a solution of sodium hydroxide (165 g, 4.1 mol) in water (1 L) is heated at reflux for 1 h, then cooled in an ice water bath. Concentrated hydrochloric acid (350 mL) is added dropwise, the precipitate collected by filtration, rinsed with ice water (3 ×), and dried in a vacuum oven at 75° C. to afford 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (125 g). m.p. 269-270° C.

Aufarbeitung

  1. temperatureAfter cooling to ambient temperature
  2. filtrationthe mixture is filtered
  3. washthe solid is rinsed with ethyl acetate
  4. concentrationthe filtrate concentrated in vacuo
  5. additionWater (2 L) is added
  6. extractionthen extracted with ethyl acetate (2×2 L)
  7. washthe combined organic extracts are washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-f5ee03f3172f46ef8f01ee844c51f926
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06515140B2

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